The indigenous microbiota of the mouth and other mucosal surfaces exists in homeostasis with the host except when perturbed, the mucosal surface damaged or the immune system compromised. Then, commensal bacteria are capable of causing severe opportunistic infections. Adaptive humoral immunity at mucosal surfaces principally is effected by secretory immunoglobulin A (SIgA) that is thought to play a role in the regulation of commensal bacteria. However, despite the fact that saliva contains SIgA antibodies reactive with commensal bacteria, these microorganisms colonize and persist on mucosal and tooth surfaces. This suggests that indigenous oral bacteria are unaffected by, not subjected to, or are able to avoid immune elimination by mucosal antibodies. This assertion is supported by data published by others showing that the acquisition and composition of the oral and intestinal indigenous microbiota of mice lacking mucosal SIgA and their litter mates do not differ, and that colonization of mice by commensal enteric bacteria appears to generate a self-limiting mucosal immune response resulting in a state of chronic hypo-responsiveness. During the previous funding period we have demonstrated, in a longitudinal study of human infants from birth to two years of age, that the commensal oral bacterium, S. mitis biovar 1, induces a limited antibody response in saliva with salivary SIgA antibodies reactive with this bacterium showing a significant decline from birth to two years of age. Furthermore, this bacterium demonstrated extensive genetic diversity and evidence of clonal replacement. Concomitantly, Western blots of envelope antigens of type strains of this bacterium showed a similar high degree of variability. In this competing continuation, the hypothesis to be tested is that commensal bacteria persist in the mouth by inducing a limited salivary SIgA antibody response due to antigenic variation mediated via clonal replacement. Employing a longitudinal study of infants from birth to 12 months, the Specific Aims are to (1) analyze the clonal diversity of S. mitis biovar 1 obtained from shedding surfaces within the infants' mouth and (2) analyze the diversity of SIgA antibodies in each infants' saliva reactive with their own S. mitis biovar 1 isolates. This work should provide important information concerning colonization of the human mouth by pioneer bacteria and may demonstrate the ability of SIgA to influence the presence of specific bacterial clones.